Diabetes is related to both genetic and environmental factors. While obesity and physical inactivity are dominant etiologic factors, exposure to environmental chemicals may also contribute to risk. Persistent organic pollutants (POPs) such as dioxins, polychlorinated biphenyls (PCBs), p,p'-diphenyldichloroethene (DDE), and polybrominated biphenyl ethers (PBDEs) are detectable in most of the US population. Recently, general population exposures to POPs, such as dioxins, PCBs, and DDE, have been associated with type 2 diabetes in several cross sectional studies and PCBs were associated with diabetes in one prospective study. The proposed project will build upon 15 years of research observation of a POP-exposed, aging cohort of Great Lakes sport fish consumers, who are at higher risk of exposure to PCBs and related compounds. POPs were measured in 947 participants at various times between 1994 and 2005. Follow up of 471 participants shows a strong association of DDE with incident diabetes. The new study will expand data on confounding variables and extend follow up of the cohort for incident diabetes, increasing the number of incident cases and the power to detect effects of PBDEs and gender specific effects of DDE and PCBs;evaluating effect modification among multiple exposures and adiposity;and determining if the association of DDE and diabetes remains significant in participants with incident diabetes more than 10 years after exposure measurements. Associations of POPs with biomarkers of diabetes risk will be investigated by testing banked serum samples for adiponectin, C reactive protein, glutamic acid decarboxylase antibodies, and 3-glutamyl transferase. The proposed research allows for efficient follow up of important findings in a well defined cohort, and will provide insight into promising avenues for future epidemiologic and toxicologic investigations on the effect of environmental exposures on diabetes. It will be the first prospective diabetes study for DDE and PBDE exposure and will be the first study of to investigate biomarkers of diabetes risk and DDE exposure. Given the ubiquitous exposure of human populations to POPs and the increasing incidence of diabetes, investigations that further delineate the role of these potentially modifiable environmental agents are important for prevention of diabetes. PUBLIC HEALTH RELEVANCE: Project Narrative This investigation will study the effect of exposure to environmental pollutants on development of diabetes. The chemicals under study are polychlorinated biphenyls (PCBs), dioxins, polybrominated biphenyl ethers (PBDEs), and p,p'-diphenyldichloroethene (DDE), a metabolite of the pesticide DDT (dichlorodiphenyltrichloroethane). It is important to find out if exposure to persistent pollutants is related to the development of diabetes because most of the population is exposed to small amounts of these chemicals.